5 Answers
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Update: nowadays, in Safari 5.1 on OS X 10.6, all keys seem to work for both Ctrl and Command, including Command-B and Command-I. I guess an update on Safari has fixed this; on an OS X 10.5 Safari 5.0.5 still showed the old behaviour, but not after I now updated it to 5.0.6.

Oddly enough, in Safari: Command-L does work (a tiny bit annoying, as I'm used to that to go into the location bar, but that's not happening a lot when I've started typing something). And so do Command-Q and Command-H (more annoying, as those are Quit and Hide on a Mac). Also: Command-G, Command-K, Command-O and others.

But, in Safari: not so much for bold and italic.

So: maybe Safari is only listening to keys that normally have some other meaning, and ignoring anything that Safari does not know about? If true, then map Command-B and Command-I to some of Safari's menu items, and you're settled.

To clarify off-hand, there was a WebKit bug that prevented Command + B, Command + I, and Command + A events from being raised in certain scenarios, because Safari was trying to use them for its own formatting shortcuts. To my knowledge, this was fixed sometime last year, but it seems that maybe the changes weren't pulled into Safari until recently.
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Tim StoneAug 6 '11 at 13:45

This web app should not be hijacking my ⌘ key! That key is for commands sent to the native application, in which a website happens to be displayed. You want ⌘-Q to be "blockquote"? ⌘-O to start a list? These key combinations have established meanings for which I (and plenty of other users) have decades of muscle memory. It's bad enough Control-B (emacs for "move back a character", which you can use in text editing on Mac OS X) gets commandeered for "mark up bold text". There's no way a web app should be changing the fundamental key bindings of my OS.

Also, it's likely that the OS will capture Command-key equivalents before the application does. It's very rare to be able to use ⌘-Any key combination on websites. I don't think most users will expect it.

Besides, should you just be writing markdown? :-)

EDIT: I can confirm this does work in Chrome for Mac... Meaning I change my position. This should be fixed to be made uniform. Either support it uniformly, or don't.